Modulation of cAMP microdomains to treat heart failure
- Funding ID
81Z2710108
- Project number
485
- Institution
- Universitätsklinikum Hamburg-Eppendorf
- Project leader
- Viacheslav Nikolaev
- Site
- Hamburg/Kiel/Lübeck
- Short description
-
The ubiquitous second messenger cAMP plays central roles in the regulation of cardiac function and diseases such as hypertrophy and heart failure. Especially the stimulation of …
The ubiquitous second messenger cAMP plays central roles in the regulation of cardiac function and diseases such as hypertrophy and heart failure. Especially the stimulation of cardiomyocyte ?-adrenoceptors leads to strong contractile response and disease progression, while other membrane receptors coupled to the stimulatory G-protein (Gs) play less prominent role. Beta-blockers are therefore central to the therapy but lead to non-cardiac side-effects which limit patient compliance. This project will test the hypothesis that cardiomyocyte-specific delivery of a dominant negative Gs mutant should provide beneficial antihypertrophic effect without systemic side-effects. This mutant will be studied in mouse diseased models and introduced into AAV for gene therapy studies.
- Project type
- Partner Site Projects
- Keywords
- cAMP, microdomains, hypertrophy, beta-blocker, AAV, genetherapy
- Topic
- cardiac hypertrophy/remodeling
- Funding
- € 491.801,84
- Begin
- 29.10.2014
- End
- 31.12.2018